Clinical question and answer: A patient had a carbamazepine level of 17. How likely is it that that level would result in severe toxicity or be life threatening?

Question:

A patient had a carbamazepine level of 17. How likely is it that that level would result in severe toxicity or be life threatening?

Additional Information/clarification:

A patient had a carbamazepine level of 17. We don't know how long after ingestion of the last dose the blood was taken. How likely is it that that level would result in severe toxicity or be life threatening? - Is there any evidence about what proportion of patients with a properly taken blood at that level would have any side effects even minor? Is it possible that level was simply found on a post - dose blood sample? If that level was sufficient to be toxic, would the LFTs usually be abnormal as well?

Answer:

It was not possible to completely answer this question by reviewing the available evidence. We would therefore recommend that you contact your local toxicology department.

  • The reference range for carbamazepine is mg/L 2-10 (Note that reference ranges may vary between laboratories.)

GP Notebook http://www.gpnotebook.co.uk/simplepage.cfm?ID=369492035&linkID=8173&cook=yes

  • The GP Notebook section on carbamazepine side effects says they are dose-related, but individual side-effects and the relevant dosages/serum levels are not provided.

GP Notebook http://www.gpnotebook.co.uk/simplepage.cfm?ID=1093992467&linkID=8171&cook=yes

  • Carbamazepine toxicity may result from acute overdose or chronic therapy.
  • Therapeutic levels are 4-12 mg/L, but individual variation exists.
  • Carbamazepine levels greater than 85 mg/L were associated with severe toxicity.
  • Ataxia and nystagmus may occur at levels greater than 10 mg/L.
  • Cardiovascular effects are usually seen at levels greater than 12 mg/L. The drug interferes with action potentials in Purkinje fibers and the His bundle, which may lead to atrioventricular blocks and arrhythmias.
  • Peak serum levels with controlled release formulations of carbamazepine can result in delayed presentations of toxicity. Levels may not peak for 96 hours from the time of ingestion.

eMedicine http://www.emedicine.com/emerg/topic77.htm

  • Initial serum levels of more than 35 mg/L (127 mmol/L) suggest serious toxicity. However, lower initial serum levels do not indicate a benign course; thus, serial monitoring is required.

eMedicine http://www.emedicine.com/ped/topic2732.htm

  • Liver function tests should also be performed before commencing treatment and periodically thereafter, particularly in patients with a history of liver disease and in elderly patients. The drug should be withdrawn immediately in cases of aggravated liver dysfunction or acute liver disease.
  • Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.
  • The combination of lithium and carbamazepine may cause enhanced neurotoxicity in spite of lithium plasma concentrations being within the therapeutic range.

Novartis SPC for Tegretol http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?DocumentID=1328

Background:

The NICE bipolar disorder guideline states:


Initiating carbamazepine
- Carbamazepine should be used for the long-term treatment of bipolar disorder only after consulting a specialist.
- The dose of carbamazepine should be increased gradually to reduce the risk of ataxia
 - When initiating carmabazepine as long-term treatment, patients should have their height and weight measured, and have a full blood count and liver function tests.


Monitoring carbamazepine
- Plasma levels of carbamazepine should be measured every 6 months to exclude toxicity, because therapeutic levels and toxic levels are close.
- Liver function tests and a full blood count should be repeated after 6 months’ treatment with carbamazepine, and weight should be monitored in patients who gain weight rapidly.
- Blood urea and electrolytes should be measured every 6 months after starting treatment with carbamazepine to check for hyponatraemia.
- Possible interactions of carbamazepine with other drugs, including oral contraceptives, should be monitored closely, particularly if the patient starts a new medication.


Stopping carbamazepine
- The dose of carbamazepine should be reduced gradually over at least 4 weeks to minimise the risk of destabilisation.
Risks associated with the use of carbamazepine
- When prescribing carbamazepine for patients taking concomitant medications – for example, people older than 65 years and people with multiple physical problems – prescribers should be aware that carbamazepine has a greater potential for drug interactions than other drugs used to treat bipolar disorder.

Search strategy:

  • NLH mental health specialist library – browsed to bipolar disorder section
  • GP Notebook – carbamazepine toxicity (12 hits)
  • eMedicine - carbamazepine toxicity (40 hits)
  • Google - carbamazepine toxicity